The epidermis is an excellent model system for the study of differentiation and carcinogenesis. Epidermal differentiation is a genetically programmed sequence of morphological and functional events in which there is a rapid turnover of distinct cell populations. In other tissues, alterations in the cell membranes have been found to be associated with stages of differentiation and with neoplasia; it has been further postulated that cell membranes may play a key role in the regulation of differentiation. Separated populations of epidermal cells will be reacted with specific surface labels including lectins, in order to characterize the major glycoproteins present on the external surface of the membrane of intact viable cells. Membrane preparations will be electrophoresed on SDS-polyacrylamide gels and reacted with radiolabelled lectins; the glycoproteins will then be isolated by affinity chromatography on lectin columns. Purified glycoproteins will be injected into rabbits to produce antibodies. These procedures will be carried out for normal cell populations at different stages of differentiation and with basal cell carcinoma and squamous cell carcinoma. For a particular population, radioimmunoassays with the specific antibody and 1251 labelled antigen will assess the extent of cell surface shedding. Radioimmunoassays will also be used to measure the cross-reactivity of antibodies and antigens drawn from different cell populations, normal and neoplastic. The overall aim is to characterize surface glycoproteins, and to explore distinctions among glycoproteins, from normal cell populations at various stages of differentiation and from carcinomas, that might serve as markers of these populations.